Clinical, radiographic and biochemical characteristics
of adult hypophosphatasia
Received: 27 August 2016 /Accepted: 10 May 2017 /Published online: 25 May 2017
International Osteoporosis Foundation and National Osteoporosis Foundation 2017
Summary In this study, we report on clinical, radiographic and
biochemical characteristics of 38 patients with adult
hypophosphatasia. High-resolution peripheral quantitative
computed tomography showed alterations of bone microstruc-
ture in a subgroup of 14 patients. Pyridoxal-5-phosphate
levels correlated with the occurrence of fractures and the num-
ber of symptoms.
Introduction Hypophosphatasia (HPP) is a rare disorder with
a wide range of clinical manifestations. A reduced enzymatic
activity of alkaline phosphatase (ALP) is the key marker of the
disease, causing an accumulation of ALP substrates such as
pyridoxal-5-phosphate (PLP). The purpose of this retrospec-
tive study was to further characterize adult onset HPP.
Methods We assessed clinical, radiographic and laboratory
characteristics of 38 adult patients with HPP. Diagnosis of
HPP was established by the combination of low-serum ALP,
raised PLP levels and typical symptoms and was genetically
confirmed in 32 patients. Dual-energy X-ray absorptiometry
(DXA) and laboratory data were available in most patients.
High-resolution peripheral quantitative computed tomogra-
phy (HR-pQCT) was performed in 14 patients.
Results Clinical characteristics included a wide spectrum of
symptoms. A history of fracture was present in 15 patients
(39%). Twenty-one patients (55%) complained about recur-
ring headaches, 23 patients (61%) had recurring muscle pain,
4 patients (11%) suffered from severe muscle weakness and
18 patients (47%) showed dental abnormalities. Z-scores
assessed by DXA were only slightly reduced in most adult
HPP patients. HR-pQCT of 14 patients showed microstructur-
al changes of trabecular and cortical bone compared to refer-
ence values of healthy subjects. The occurrence of fractures
and multiple symptoms (>2 typical HPP symptoms) were as-
sociated with significantly elevated levels of PLP.
Conclusion Adult HPP presents with a wide range of clinical
symptoms and is not associated with low bone mass in gener-
al. PLP seems to be a good marker for disease severity in adult
patients as its level is correlated with the occurrence of frac-
tures and number of symptoms.
Keywords Alkaline phosphatase
Rare bone diseases
Hypophosphatasia (HPP) is a rare inherited disease caused
by mutations of the TNSALP (ALPL) gene , resulting in
the reduction of tissue-non-specific isoenzyme of alkaline
phosphatase (TNSALP) activity. The prevalence of severe
forms is estimated at between 0.3 and 1/100,000 .
However, recent studies suggest that moderate forms, in-
cluding those of adults, might be substantially more fre-
quent [3, 4]. Persistent hypophosphatasaemia was found in
1/1544 adult patients seen at a major medical centre in the
USA . More than 300 mutations of ALPL have been
described and are collected in the ALPL gene mutation
Electronic supplementary material The online version of this article
(doi:10.1007/s00198-017-4087-z) contains supplementary material,
which is available to authorized users.
* T. Schmidt
Department of Osteology and Biomechanics, University Medical
Center Hamburg-Eppendorf, Lottestraße 59,
22529 Hamburg, Germany
Department of Orthopaedic Surgery, University Medical Center
Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany
Osteoporos Int (2017) 28:2653–2662